The peptide chain elongation factor EF-Tu is a GTP regulatory protein whose interactions with a variety of cellular components make it an informative subject both for the study of nucleoside triphosphate-promoted processes and for the identification of protein-protein and protein-nucleic acid interactions. EF-Tu presents a useful model for these processes because it is an abundant, soluble protein of tractable size whose tertiary structure has been largely solved, and because its amino acid sequence shows extensive homology to other GTP-regulatory proteins. By X-ray crystallography three regions of the protein appear to interact with GDP: amino acid residues 20-27, 80-85, and 134-138. These regions show sequence homology in all GTP regulatory proteins thus far examined. These residues can be altered by site-directed mutagenesis to yield proteins possessing altered activities. By measuring the activity of each altered EF- Tu in binding EF-Ts, GDP, GTP, aatRNA and ribosomes, each amino acid's functional importance can be quantitatively evaluated. Such studies are already in progress on the Harvey-ras 1 p21 protein, and may be completed for the adenylyl cyclase regulatory proteins, transducin, and other protein synthesis factors. Although tertiary structure models for these proteins in lacking, one can correlate these functional data to the EF-Tu model after the homologous alterations on EFTu have been evaluated. The regions of the protein involved in binding tRNA, EFTs and ribosomes are currently unknown. These are being identified by chemical crosslinking and functional analysis of truncated EF-Tu molecules. Specific amino acid residues in these regions will then be altered to assess their contributions to these activities.